A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants
| Autor: | Chawner, Samuel JRA, Doherty, Joanne L, Anney, Richard JL, Antshel, Kevin M, Bearden, Carrie E, Bernier, Raphael, Chung, Wendy K, Clements, Caitlin C, Curran, Sarah R, Cuturilo, Goran, Fiksinski, Ania M, Gallagher, Louise, Goin-Kochel, Robin P, Gur, Raquel E, Hanson, Ellen, Jacquemont, Sebastien, Kates, Wendy R, Kushan, Leila, Maillard, Anne M, McDonald-McGinn, Donna M, Mihaljevic, Marina, Miller, Judith S, Moss, Hayley, Pejovic-Milovancevic, Milica, Schultz, Robert T, Green-Snyder, LeeAnne, Vorstman, Jacob A, Wenger, Tara L, IMAGINE-ID Consortium, Hall, Jeremy, Owen, Michael J, van den Bree, Marianne BM |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Heterozygote DNA Copy Number Variations Autism Intellectual and Developmental Disabilities (IDD) Severity of Illness Index Copy Number Variants Medical and Health Sciences Risk Factors Clinical Research Behavioral and Social Science Prevalence Genetics Humans 2.1 Biological and endogenous factors Genetic Predisposition to Disease Interview Genetic Testing Autistic Disorder Aetiology Child Genetic Association Studies Pediatric Psychiatry Prevention Human Genome Psychology and Cognitive Sciences IMAGINE-ID Consortium Brain Disorders Mental Health Psychological Gene Deletion |
| Zdroj: | The American journal of psychiatry, vol 178, iss 1 |
| Popis: | ObjectiveCertain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.MethodsThis international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.ResultsThe four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.ConclusionsMany CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant. |
| Databáze: | OpenAIRE |
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